Monday, February 19, 2007

Surgery May Aid Bladder Control After Spinal Cord Injury

Needing a wheelchair isn't always the biggest complaint of people left paralyzed by spinal cord injury - it's also the loss of bladder control. Recently, Michigan doctors began a unique experiment to see if rerouting patients' nerves just might fix that problem.

It's a delicate operation: Surgeons cut open a spot on the spine and sew two normally unrelated nerves together ---- one from the bladder to one from the thigh ---- with a single hair-thin stitch. It will take months for this new nerve bridge to heal, an anxious waiting period for the first volunteers.

But if it works, merely scratching the thigh should signal the bladder to empty, allowing patients to ditch their despised catheters and restore a longed-for degree of freedom, as well as fewer bladder infections and other serious complications.

"I've got nothing to lose by doing this," is the way a cautiously hopeful Kevin Bryant, 19 and paralyzed from the waist down by a car crash, approached the experiment.

It's a technique pioneered in China that is starting to garner international attention ---- and surgeons at William Beaumont Hospital in Royal Oak, Mich., hope their new U.S. study will prove if the approach really is a solution for at least some patients.

"We're very excited," says Dr. Kenneth Peters, Beaumont's urology research chief, who headed a team of doctors that traveled to China last February to watch Dr. Chuan-Gao Xiao operate at the Huazhong University of Science and Technology.

"We said, 'This is something we need to study ... to see if we can reproduce this in the U.S.,"' adds Peters, who in turn invited Xiao into Beaumont's operating room. If the results hold up, "it would allow us to treat those patients who have no other alternatives."

Monday's first volunteer: a 49-year-old paralyzed from a car crash, Kevin Conkey of Fenton, Mich. Bryant, the 19-year-old paraplegic, was also set to undergo the procedure ---- in addition to a child with spina bifida, an improperly formed spinal cord that can cause similar bladder dysfunction.

After infancy, the brain takes over control of urination. The bladder sends "I'm full" signals up the spinal cord. Once the person's in an appropriate spot, the brain signals back to the bladder to empty.

In spinal cord injury and spina bifida, that control is disrupted, leaving patients either unable to urinate or constantly wet. They depend on catheters to empty the bladder every few hours. Still, recurrent infections and even lifethreatening kidney damage from backed-up bladders are common, not to mention the inconvenience and even embarrassment the procedure brings.

"People put so much emphasis on walking. I don't care if I walk again; that's not the No. 1 thing," says Bryant, of Rochester Hills, Mich. Going to the bathroom is "such a hassle in day-to-day life. I have to schedule my life around the times when I'm going to catheterize."

Xiao's procedure can't restore sensation, but uses intact nerves below the spinal injury to try to create a reflex that bypasses the brain.

"Thinking over the (urination) process, its final step is just a signal to the bladder to contract," Xiao explained in an e-mail interview. "Can we find another way to send a signal to initiate bladder contraction and voiding?"

First, surgeons remove a piece of bone alone the lower spine to expose spaghetti-like nerve roots beneath. They reconnect a lumbar nerve responsible for thigh sensation to a sacral nerve that would normally open the bladder.

It can take a year, maybe longer, for the two nerves to grow together, and people with certain bladder or spine scarring aren't candidates.

But Xiao says 110 spinal cord injury patients and 230 with spina bifida have undergone the procedure, including two at New York University where he began the research years ago. He has reported a fraction of those cases in respected urology journals, suggesting about 80 percent resume voiding eventually.

In the Michigan study, doctors plan to suspend operating after six or eight patients, to resume only once, if, there are signs of success.

"I'm surprised that more people haven't done this before," says Dr. John McDonald, spinal cord injury chief at the Kennedy Krieger Institute and a former physician for the late Christopher Reeve.

He calls the method a logical next step from nerve-grafting for other injuries that takes advantage of primitive bladder reflexes at the spine's base. "It's very reasonable to take this approach with the bladder."

"As a field, neuroscience is revisiting the adaptive capabilities of the spinal cord below the level of the injury," agreed Dr. John Martin, a neurobiologist at Columbia University Medical Center ---- but who cautioned patients to await the research. "Some of these ideas that look good haven't come to fruition."

There are some risks, Peters cautioned, including general anesthesia and wound infections. For children with spina bifida who can walk, rerouting the thigh nerve causes a small risk of some foot weakness.

And it will be expensive, about $30,000 to $40,000 a person, he estimated, a tab Beaumont is funding through a private donor.

Study information: http://www.clinicaltrials.gov/ct/show/NCT00378664?order1, or potential volunteers may call 1-248-551-3355.

By: LAURAN NEERGAARD
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Paralyzed Men Can be Fathers

In the weeks following the car accident that left him paralyzed below the waist, Geoff Luther was haunted by worries that he'd lost the chance to be a father.

Then 27, he hadn't yet fallen in love with the woman of his dreams. When he did, he wanted to start a family with her. But how?

"It was some of the stuff I was thinking about the most," said Luther, who rolled his S-10 Blazer on black ice. "What about having children? What about getting married? Can you naturally conceive a family?"

His questions are shared by thousands of young men each year who suffer paralyzing spinal injuries. But many may give up hope - or undergo unnecessary, invasive procedures - because their doctors don't know about simple ways to help them.

Doctors at the Rehabilitation Institute of Chicago told Luther, now 43, that most men with spinal cord injuries can father children. But the treatments that allowed Luther and his wife, Tammy, 38, to conceive aren't offered to many injured men.

Instead some fertility doctors jump immediately to expensive, invasive procedures, such as surgically extracting sperm from the testes, when confronted by a man in a wheelchair.

The Luthers, who live in Oak Brook, Ill., avoided that procedure. Nonetheless, it took six years and, they acknowledge frankly, tens of thousands of dollars before they succeeded. But after a tour through most of the methods and procedures of rehab fertility medicine, the Luthers conceived their son, Trent, now 6, and daughter Kayla, now 3.

"We went through it all," Tammy Luther said.

Their story illustrates how determined couples can conceive with guidance from medical professionals who are well-versed in techniques that work for paralyzed men.

Unfortunately, many fertility centers don't know the basics.

Nancy Brackett, a researcher at the Miami Project to Cure Paralysis, surveyed more than 100 fertility centers and discovered that 28 percent don't offer two simple techniques that rehab experts have used successfully for years and that work for 95 percent of paraplegic and quadriplegic men. Brackett published her findings in the October issue of Fertility and Sterility, a journal read by reproductive medicine doctors, and now she has made the issue her soapbox.

Most men with spinal cord injuries have varying degrees of difficulty with erection and ejaculation. Medications like Viagra help some. Others need only a special vibrator to collect sperm; insemination of their partners can be done with a syringe in private, at home.

Paul and Shelly LeVasseur of Winfield, Ill., felt lucky they could conceive at home.

"There are times when it is rather clinical and there are times when it is very romantic," Paul LeVasseur said. Their children are Ben, 6, and Danielle, 2, and they are trying for another.

Other injured men require a different device that that triggers ejaculation with a low-voltage impulse of electricity, a procedure borrowed from animal husbandry and developed for use in humans by Dr. Carol J. Bennett and her colleagues in University of Michigan's urology department.

Geoff Luther remembers asking his doctor: "How will you know when you have it turned up high enough? Will my ears start smoking or what?"

That technique worked for Luther, but his sperm quality was low. So, a single sperm was injected into one of Tammy's eggs to create an embryo. The resulting embryo was implanted in Tammy's womb and, finally, she was pregnant.

"I loved being pregnant," she said.

Brackett wants doctors to try simple solutions before assuming they must use surgical means to retrieve sperm from the testes of injured men. In her survey, some doctors said they lacked training or equipment, or were unfamiliar with the methods.

"If we forget these simple things, it's almost like going backward," Brackett said. "It does a disservice to these patients."

Of the 11,000 spinal cord injuries annually in the United States, 80 percent are among men between the ages of 16 and 45 - the prime reproductive years.

Rehabilitation Institute nurse practitioner Diane Rowles, who teaches a class called Sexuality and Fertility to patients, said sex is "a very private topic, a very personal topic." But if medical staff don't educate spine injury patients about sex and fertility, they may assume the worst: that they're not able to have a sex life or father children.

"It's a big thing. You just can't leave it out," Rowles said. "They need to learn about it, too."

The Luthers' children haven't asked where babies come from. Tammy Luther said someday, if they ask, she'll tell them about many different ways children come into the world, from adoption to reproduction with medical help.

Geoff Luther said he doesn't know what he would say. "I still haven't had that talk with my mom and dad, so I'm not sure," he said.

He does know what he would say to any man with a spinal cord injury who wants to be a father: "Search out the best doctors, or you can waste a lot of time and resources."

By Carla K. Johnson
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'Smart Bladder' Pacemaker Could Help Paralyzed

Duke University researchers say they've moved a step closer in their efforts to develop a 'smart bladder pacemaker' that could restore bladder control in people with spinal cord injury or neurological diseases.

The latest finding of the project, which started in 2004, shows that electrical stimulation of the pelvic nerve in the spinal cord can control the contraction and relaxation of muscles involved in bladder control.

In tests on cats, the researchers found that high frequency electrical pulses directed at the pelvic nerve helped empty the bladder, while low frequency pulses increased bladder capacity and improved continence.

This method of manipulating the nervous system is a more flexible way of controlling urinary function than direct bladder stimulation, said Warren Grill of Duke's Pratt School of Engineering.

"Stimulating the bladder directly can cause it only to contract, not to keep it from contracting. We stimulate the sensory inputs in the spinal cord to orchestrate either the inhibition or activation of urination," Grill said in a prepared statement.

"This illustrates an important principle: We can use the 'smarts' of the nervous system to orchestrate control of complex functions," he said.

It may be possible to use a similar approach to stimulate spinal reflexes that control movement to help people who are paralyzed, Grill said.

The research is expected to be presented Friday at the American Association for the Advancement of Science annual meeting in San Francisco.
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Thursday, February 15, 2007

Human Stem Cell Transplants Repair Rat Spinal Cords

Human nerve stem cells transplanted into rats' damaged spinal cords have survived, grown and in some cases connected with the rats' own spinal cord cells in a Johns Hopkins laboratory, overturning the long-held notion that spinal cords won't allow nerve repair.

A report on the experiments will be published online this week at PLoS Medicine and "establishes a new doctrine for regenerative neuroscience," says Vassilis Koliatsos, M.D., associate professor of neuropathology at Johns Hopkins. "The spinal cord, a part of the nervous system that is thought of as incapable of repairing itself, can support the development of transplanted cells," he added.

"We don't yet know whether the connections we've seen can transmit nerve signals to the degree that a rat could be made to walk again," says Koliatsos, "We're still in the proof of concept stage, but we're making progress and we're encouraged."

In their experiments, the scientists gave anesthetized rats a range of spinal cord injuries to lesion or kill motor neurons or performed sham surgeries. They varied experimental conditions to see if the presence or absence of spinal cord lesions had an effect on the survival and maturation of human stem cell grafts. Two weeks after lesion or sham surgery, they injected human neural stem cells into the left side of each rat's spinal cord.

After six months, the team found more than three times the number of human cells than they injected in the damaged cords, meaning the transplanted cells not only survived but divided at least twice to form more cells. Moreover, says Koliatsos, the cells not only grew in the area around the original injection, but also migrated over a much larger spinal cord territory.

Three months after injection, the researchers found evidence that some of the transplanted cells developed into support cells rather than nerve cells, while the majority became mature nerve cells. High-powered microscopic examination showed that these nerve cells appear to have made contacts with the rat's own spinal cord cells.

The research was funded by the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association and the Robert Packard Center for ALS Research at Johns Hopkins.

Authors on the paper are Jun Yan, Leyan Xu, Annie M. Welsh, Glen Hatfield and Koliatsos, all of Hopkins, and Thomas Hazel and Karl Johe of Neuralstem of Rockville, Md.

Note: This story has been adapted from a news release issued by Johns Hopkins Medical Institutions.
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Scientist Offers Hope for Spinal Cord Repair

A Dalhousie University scientist and his colleagues have discovered a "volume knob" for the brain when it tells the body to walk.

The finding reveals a new aspect of the complex neurological system that could one day improve treatment for spinal cord injuries and diseases like amyotrophic lateral sclerosis, said Dr. Robert Brownstone, a neurosurgeon and professor of anatomy and neurobiology.

It is already known that the brain relies on cells called motor neurons to translate messages like "walk" or "turn" into action.

"When we walk, our brain has better things to do than to think about which muscles to control," Dr. Brownstone said Monday. "Those motor neurons can be getting the signals, but unless the volume is turned up, they?re not going to produce movement. Essentially what we?ve found here is kind of like a volume knob within the spinal cord."

Dr. Brownstone and colleagues Gareth Miles of the University of St. Andrews, who studied in the Dal lab, and Andrew Todd and Robert Hartley of the University of Glasgow in Scotland described the system of spinal interneurons they discovered. Their findings are outlined in the journal Proceedings of the National Academy of Sciences of the United States of America.

A few interneurons in the spinal cord act to amplify signals from the brain to many motor neurons.

Mr. Miles demonstrated that when these cells in mice are activated, the electrical output from the motor neurons, telling muscles to contract in response to chemical signals from the brain, is much larger than when the cells are not activated.

Because the interneurons related to walking are located in the lower back, they?re typically unaffected by spinal cord injuries.

Many people working on repairing the spinal cord are seeking ways to grow severed nerve fibres across injury sites, Dr. Brownstone said. But the fibres need to know where to go and what to do.

He said discoveries like this one, supported by funding from the Canadian Institutes of Health Research, offer hope that re-establishing even a small connection across an injury site could be enough to get messages from the brain to the rest of the body when these amplifiers are manipulated.

Some people with spinal cord injuries experience spasms, suggesting the signal amplifiers might be set too high, Dr. Brownstone said.

Amyotrophic lateral sclerosis, or Lou Gehrig?s disease, kills motor neurons in the spinal cord, gradually robbing a person of control of their body.

"If you have fewer of them they have to work harder," Dr. Brownstone said. "Maybe we can just adjust the volume knob and make things a little easier."

The next stages of research will try to draw a more complete picture of what other actions are affected by the amplification effect of the interneurons and examine the chemical receptors on the cells to determine what drugs might be used to manipulate them, he said.

Dr. Brownstone wouldn?t speculate when such treatments might be possible for people with spinal cord injuries or neurological disease, though he said collaborations like this one, with experts in Glasgow, help speed the process.

"Progress is much quicker now than it was 10 or 15 years ago," he said. "But the last thing we want to do is move too quickly."

By JOHN GILLIS
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Study: Spinal Cord Can Repair Itself

U.S. scientists say they have disproved the long-held theory that the spinal cord is incapable of repairing itself.

The Johns Hopkins University researchers say human nerve stem cells they transplanted into damaged spinal cords of rats have survived, grown and in some cases connected with the rats' own spinal cord cells.

The accomplishment "establishes a new doctrine for regenerative neuroscience," said Dr. Vassilis Koliatsos, an associate professor of neuropathology.

"We don't yet know whether the connections we've seen can transmit nerve signals to the degree that a rat could be made to walk again," he added. "We're still in the proof-of-concept stage, but we're making progress and we're encouraged."

The research, conducted by Jun Yan, Leyan Xu, Annie Welsh, Glen Hatfield and Koliatsos, appears online in the journal PLoS Medicine.
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Monday, February 05, 2007

Iran Announces Technique to Repair Spinal Cord Injuries

Iran announces innovative new technique to repair spinal cord injuries

On Sunday, the Islamic Republic officially announced that Iranian scientists have developed a new technique for treating patients with spinal cord injuries.

In this method of Schwann cell transplantation, the Schwann cells are taken from the back of the patient?s leg (below the knee) and grown in the lab. They are then injected into the site of the injury.

Researchers from the Spinal Cord Injury Treatment Center of the Tehran University of Medical Sciences have scientifically proven the efficacy of the new method through 30 operations on humans.

?The degree of recovery is 85 percent in patients with partial paralysis, and 15 percent in patients with full paralysis,? the director of the spinal cord injury research group, Hushang Saberi, said at the ceremony held to announce the Iranian scientists? achievement.

Such transplantations are being practiced in Ukraine, China, which uses fetal and adult stem cells, and Russia, which uses dipolar nerve cells, but these techniques are risky, he added.

Thirty patients were chosen to undergo the surgery, 40 percent of whom experienced at least partial recovery as far as sensation and physical movement, with 35 percent showing no change, and 25 percent still in the initial post-surgical stage, he explained.

President Mahmud Ahmadinejad also spoke at the ceremony, saying that his administration supports the country?s research projects 100 percent.

Ahmadinejad called on Health Minister Kamran Baqeri Lankarani to make the scientific achievements swiftly and widely available to the public.

The government will pay, either directly or through insurance, for the treatment of any patient with spinal cord injuries who can not afford it, he stated.
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Friday, February 02, 2007

New Hope for Spinal Cord Injuries

Tiny nerves taken from the rib cage, fortified with a powerful growth inducer and transplanted in the spinal cord significantly reversed paralysis in rats with spinal cord injuries.

That?s the finding of a study in the October issue of the Journal of Neurotrauma.

The study shows that nerve cells can be inserted and stimulated to grow in damaged areas of the spinal cord, and the discovery may lead to improved treatments for people with spinal cord injuries.

Using this method, researchers from the University of California-Irvine (UCI) and the Long Beach Veterans Administration Medical Center were able to partially restore hind leg movement in rats with severed spinal cords.

"By using tiny nerves from the rib cage as cables connecting the severed spinal cord, we were able to get some improvement in leg function," says Dr. Vernon Lin, a professor of physical medicine at UCI and director of the Spinal Cord Injury Group at the Long Beach V.A.

"Regeneration is considered very difficult because the damaged area apparently inhibits growth of new nerve-cell connections. This study gets us closer to arriving at the right combination of growth factors, nerve cells and physical stimulation to overcome these inhibitions and successfully treat spinal cord injury," Lin says.

The growth inducer used in this study, a molecule called aFGF, is found in most nerve cells.

The rats with severed spinal cords that received both a FGF and the nerve grafts were able to move their hind legs and could support some of their weight on those legs after treatment. Rats that received either a FGF or nerve cell grafts alone had nearly no improvement, the study says.
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